MaryO'Note:This article says: Rowell did not have to have chemotherapy or radiation for his tumors because such treatments are rarely effective for his type of cancer.

I'm so glad to see that they printed this. When I tell people I didn't have chemo or radiation they think that means my cancer wasn't a serious one and they dismiss it. It's nice to have this bit of validation!

DUNCAN — Billy Rowell enjoys Christmas. In fact, the Duncan pastor enjoys every day of the year because it wasn’t too long ago that he thought those days might be coming to an end.

A self-employed carpenter and pastor of Grace Baptist Church, Rowell’s life was fairly routine, revolving around work, his church and family. He’s lived east of Duncan all his life, and graduated from Comanche High School in 1978. Rowell served as youth minister at the church for three or four years, as song leader for a year or two, then became its pastor almost two years ago, succeeding his father-in-law, the Rev. Bill Florez, who was pastor for many years.

Early in 2003, however, he began to have some “minor” health concerns. A trip to his doctor proved to be an eye-opener and the beginning of a long journey through the valley of the shadow of death to a new appreciation of life and a realization of the many blessings that life bestows.

“I was diagnosed with renal cell carcinoma — cancer — in my left kidney. That was a shock. I now know how people feel when they hear the ‘C-word.’ My kidney was removed in March of 2003 in Lawton, just before my 43rd birthday.

“My prognosis was good until July 2004. You know, when you have a serious illness like that, they watch you carefully. I had check-ups every three months, and PET scans, and they’d give me a good going-over. In July of that year, the tests showed two spots, lesions, I guess you’d call ’em, on my liver.” A fairly new technique called radio frequency ablation literally “zapped” the liver spots away, and Rowell thought he was home free until his doctor walked into his hospital room. “He said, ‘The liver is OK, but I found a tumor in your right kidney.’ I knew then that I was in trouble,” Rowell said. Because Rowell had already lost one kidney, it was vital that his remaining kidney be saved, if at all possible. The tumor was removed but the kidney was severely damaged. What followed was a miserable year of bleeding, inability to work, pain, 23 times under anesthesia and four major surgeries.

“I have three scars over 14 inches long each on my gut. When they have to make an incision like that, they make the cut through all the muscles and stuff and then insert this huge stainless steel ring to stretch the opening and give them room to work. It takes a long time to recover from something like that,” he said. During 2005, Rowell had at least one hospital stay every month except for April and May. The attempts to save his remaining kidney were making him really sick, he said.

“I learned then that Duncan is one of the greatest cities in the world. I love the people of Duncan. The whole community pitched in to support us with prayers and donations. One anonymous donor alone gave $16,000. Some oil field workers in Velma held a golf tournament and raised over $9,000. The outpouring was amazing.

“I’m so grateful for all the prayers. A man in Iowa learned about me on the Internet and put my name in a Catholic prayer chain that went to computers all over the world. Me, a Baptist preacher, and Catholics I never knew were praying for me. I’ve seen how God works, and it’s miraculous!”

Finally, his remaining kidney failed and had to be removed at OU Medical Center.

“My right kidney was the first known kidney to have been removed with radio frequency ablation. All of the surgery was done through a chest tube. A week and a half later, I was able to work again,” Rowell said.

Rowell did not have to have chemotherapy or radiation for his tumors because such treatments are rarely effective for his type of cancer.

“Not good enough odds,” he said.

“I’ve learned you had better enjoy every day you’ve got. Don’t take family or friends for granted. Life was OK before, now I love life. Faith got me through some difficult times. I feel blessed,” Rowell said.

Rowell credits his wife, Kim, with helping him get through the worst days. Kim Rowell is a human resources coordinator at Hydra-Rig. She stayed with her husband constantly during his hospitalizations, making sure he got the right medications and that his condition was carefully monitored as his disease progressed.

“She’s also got good medical insurance through her job. They don’t tell me what things cost. She and the insurance just take care of ’em.”

The couple has been married 30 years, and has two sons: Chris, 28, who lives in Blanchard, and Ryan, 26, who lives in Duncan. They also have a 19-month-old granddaughter, Brooklyn Grace, who is the apple of her grandfather’s eye.

Rowell went on kidney dialysis in March of 2005. He still takes the treatments that cleanse his body of toxins and fluids three days a week, along with about 30 pills a day. He continues his carpentry work on the days he’s not taking dialysis, and carries out his pastoral duties day and night, according to the needs of his congregation. He was ordained earlier this year.

Rowell said he’s learned some amazing things during the course of his illness.

“This body isn’t an accident. It’s too complicated not to have been made by God. It works good, too, until people mess it up,” he said.

Along with the support of his family and the overwhelming outpouring of help from the community, Rowell credits his recovery to staying positive and staying busy. While he’s taking his lengthy dialysis treatments, he talks with the people around him who are also taking treatments, and asks them how they’ve made it this far. The overwhelming response is “prayer and staying positive.”

“I want to last a while. I push myself and stay strong. You go downhill when you sit around,” he said.

“When you get a diagnosis of cancer, you’re going to have fear. You might act tough, but no matter what you do, you’re not dying until God says it’s time. Pain lets me know I’m alive. I look at things differently now.”

Rowell hopes to get on a kidney transplant list soon. He has to live nine more months cancer-free, then he can begin the lengthy testing process to get on a waiting list.

“I’m not sick. I don’t have kidney disease, I just have to depend on a machine to carry out the functions my missing kidneys would ordinarily do. I don’t feel normal, because of the poison levels in my body, but I choose to stay positive. I look forward to days. Worrying burns energy, takes away your life force. When things get to be too much for me, I just say, ‘God, you’re doing to have to deal with this.’ I don’t have to understand it all. I trust God and I know he has a wonderful place waiting for me, and that’s fine with me,” Rowell said.

As promised Sunday, here's the first of several posts I made to my kidney cancer group on ACOR.

Jargon key: NED = No Evidence of Disease. We don't say "cured" because invisible microtumors can still exist. All we can say is "no evidence of disease." Complete Responder: a patient whose disease has "completely responded" to treatment, i.e. disappeared, i.e. NED. VHL = Von Hippel Lindau syndrome - a particular form of kidney cancer (not mine). Mets = metastases (distant tumors, as opposed to the primary tumor where the cancer started).

I'm going to write some things here about foods. I'm not representing them as sure cures or treatments or anything of the sort. But, I've been doing some research and I've checked with some people I trust and I think this is worth sharing. Here's the thing: I'm an IL-2 responder whose mets have shrunk another 75% since my treatment ended 7/23/07, but my oncology team is out of advice for me. They say my odds of relapse are now down to 50%, but they have no advice on how to improve my odds. But like most people here, I'm not one to sit back and just hope! My wife bought us a book Anticancer: A new way of life by an MD/PhD who had a brain tumor, got rid of it, and had it recur, all before he was 40. Third time around he decided to look for additional advice, beyond what his doctors had said ("Eat what you like. Just don't lose weight.") (I first wrote about the book in November: Chocolate Therapy, and I just found a good layman's article about it in a British paper here.) He found there's a lot of research worth paying attention to regarding how tumors grow and what foods help or hinder them grow. Background: 1. One way cancer works is to hijack our normal inflammatory response. For one thing, an everyday injury triggers tissue repair, which includes growth of new blood vessels (angiogenesis). We can fight tumors by any intervention that discourages inflammation or angiogenesis. Some foods do that. 2. Angiogenesis plays a key role when microtumors get promoted into nastier things. (The book's cover says "All of us have cancer cells in our bodies. But not all of us will develop cancer.") It's good to interfere in that process. Note: that text explained to me why even complete responders (NED) often have a "relapse" (i.e. they go from NED to having visible tumors again). And boy is it motivating to realize I can affect THAT! Even better: in the three-step cancer growth process (initiation / promotion / progression), PROMOTION IS REVERSIBLE. I realized: holy crap, I don't have to sit here and hope some tiny death pellet hasn't already started growing?? If I catch it early, I can REVERSE it??? That's game-changing! 3. At a Christmas party I bumped into Dr. Othon Iliopoulos of Mass. General, head of their VHL program. (Heck of a party, huh?? It wasn't a medical event.) He told me fighting angiogenesis is also good against mets, whose size can be "vessel-limited." So: choose foods that resist angiogenesis, and avoid foods (particularly fats) that cause inflammation. A few specifics: 1. Green tea has powerful antiangiogenesis ingredients. Have 2-3 cups a day; steep for 10 minutes to release the goodies and drink within an hour before they expire. 2. Green tea also binds receptors that affect tissue penetration into neighboring cells. 3. Raspberries & strawberries have lots of ellagic acid, which blocks angiogenesis by acting against VEGF and PDGF. 4. Turmeric (an ingredient in curry) is a potent anti-inflammatory. Buy turmeric, not just curry (which is only 20% turmeric). Also turmeric must be taken with black pepper, and ideally dissolved in oil. 5. As many have said here, cruciform vegetables are good (Brussels sprouts, broccoli, cabbage and cauliflower). 6. Blueberries and dark chocolate (not milk chocolate!) contain proanthocyanidins, which promote apoptosis (cell death). Yes, ladies & gents, you can fight mets by eating dark chocolate! (At least 70% cacao.) I now eat it at work, declaring that I'm taking my medicine. (You should see the looks I get; people are sorta getting used to my being playful about cancer.) That brings me to a non-food item, psycho neuro immunology (a long word that I insist on breaking up): 7. It's finally been proven that humor and other mood-enhancers beneficially affect the immune system. (Psych affects neurosystem which affects immune system.) So laugh! And do meditative/prayer/yoga stuff!

More in a later post. Suffice it to say, I love being able to look at my kitchen with a sense that it's a weapon to fend off invisible future cancer events! Note, about the above: In an e-patient community, people (ordinary lay patients) become very educated about their disease, help reality-check each other, and share what they learn. This is very, very different from the isolation and lack of empowering information that plagued us just a few years ago. (See the opening anecdote of "E-Patients: How they can help us heal health care," Dr. Blakely & Mr. Murphy, which happend the same month the Web came into being.) The Internet has brought us together with each other, and has brought us together with information we might never have seen. It's let us share what we learned, reaching others who might have had even less chance of seeing it. And here's the key thing: sometimes it goes beyond what patients can get from their own oncologists – even some of the best specialists in the world. "Because," as the banner on the e-patient blog says, "health professionals can't do it alone." This is "Health 2.0" on the hoof. Here's the definition that some of us "crowdsourced" last June:

Health 2.0 is participatory healthcare. Enabled by information, software, and community that we collect or create, we the patients can be effective partners in our own healthcare, and we the people can participate in reshaping the health system itself.

And that is how it works these days. The Internet is altering the balance of power by bringing us together with information and with each other.

Tuesday, December 30, 2008

I think there must be a huge transition point when you realize that chronic relapses and remissions are going to be part of your life - with a lot of struggle and distress beforehand. Also there is the hope things will get better, with just a little more rest, etc. But then you plunge into anger and loss of what was, not knowing what exactly will be.

I continue to work part-time, but I am in a fairly constant state of low grade pain which is incredibly wearing and draining.

I've been on full disability for over 5 years, and it was an awful decision to make, but no real choice due to severity of my symptoms. I have kept my license up, hanging on to the thread of hope that some great biologic will come along and put me back in the game.

It is incredibly challenging to look well and have others expect you to function like a normal person. Most people don't know that my round face is not robustness, but Cushing's secondary to long term steroids.

I know how this doctor feels for sure. I don't have what he/she has but I know the feeling of not being able to function well.

I'm hanging on to only 2 piano students, who I usually hope will cancel - or I cancel them - but I'm scared to death of quitting teaching altogether. What if, by some miracle, I do feel better someday? In my mind I know that this is so unlikely because I've felt like this for nearly 30 years but somehow, maybe?

My temporary job is cutting into my energy, too. People just don't understand the need to nap NOW, that I can't do just this little one more thing.

My husband still doesn't get it, either. If not now, when?

I don't think at this stage of the game the Cushing's will come back but there are those aftereffects. The panhypopituitarism, low growth hormone, adrenal insufficiency followed by the removal of one of those low-functioning adrenals.

As we enjoy the last few days of 2008, and consider the year to come, I'd like to take this time to wish you a Happy New Year, and also to congratulate you for being chosen by your readers to be one of the 100 Best Health Bloggers on the Web in the People's Health Blogger Award competition!!!

The 2009 Bloggers’ New Years Resolution – Make your blog more visible and help more people live healthier, happier lives

Congratulations on being one of the 100 best health bloggers so far in the People's Health Blogger Awards competition! Your current standing in the People’s Health Blogger Awards will help you get the recognition you deserve from everyone who reads your postings and benefits from your writing both on Wellsphere and on your blog. Because of the quality of your blog, you now have a shot at winning the competition! With only a couple of weeks to go, and with more and more readers participating and voting – you are closer than ever to making it happen!

Here is what some of the current participants are saying about the competition:

"I think the competition is a fantastic way to find out about lots of people's different blogs, which I wouldn't have known about otherwise [..] The competition has also brought lots of people to my blog which is fantastic. I find writing so much more worthwhile if I know people are enjoying what I write." Holly

"It's such an honor to participate and we think the project ROCKS! What an awesome way to educate folks on worthwhile resources - and we're loving the boost in audience for ChronicBabe." Jenni

"I feel honored to be in this competition and to have people voting for my site. It is a high honor to even be listed here. I believe it has brought more attention to my site and whether I win or lose I feel like I won just being considered! Sandi B

If you are one of the few who have not yet posted your "Vote for Me" badge on the sidebar of your blog, post it now and ask your readers to vote for you (you will find your personalized badge code on your MyGoodies page at http://www.wellsphere.com/healthBloggerAwardAds.s ). Once your "Vote for Me" badge is in place, you may want to reach out to your friends and colleagues to let them know they can vote for you too. Another powerful way to get more people to see your blog and vote for you is to ask friends and colleagues who are not in the competition to post your "Vote for Me" badge on their blogs and websites—it works—ask the current leaders J

2009 Here We Come — set up a personal health goal for 2009

If you or your readers would like to set a health goal or resolution for the coming year, you might want to explore the goal setting and tracking features on Wellsphere. You may be pleasantly surprised to discover a range of functions and tools that help you set your goals, track your progress, and get support from others.

My Life With Cushing's Disease A healthcare provider shares her story. By Kathie Harrington, MA, CCC-SLP

Cushing's might sound like something soft and fluffy; but it's quite the contrary.

A rare condition that presents itself with many physical characteristics, Cushing's occurs most often in women ages 20-40, but can occur in males or in children and older adults, such as was the case for me.

I was diagnosed at 58.

I'd never heard of the disease until January 2007, when my endocrinologist confirmed some strange changes I was noticing with my body during a routine visit. He noted my "moon face" and the "buffalo hump" on the back of my neck as well as redness in my face and neck. He also realized my blood sugar levels were high even though I had been on 105 units of insulin per day due to my diabetes mellitus. My extreme fatigue was also a concern, as was my weight gain and lack of muscle strength in my arms and legs.

John Carmichael, MD, and Kathie at Cedars-Sinai, June 14, 2007.

Facing The Realization When I was diagnosed, I was scared. After an MRI revealed a tumor on my pituitary gland it didn't take me long to realize that Cushing's is a very serious, life-threatening condition. But I also learned it often goes undetected and, thus, untreated. All healthcare professionals should know the signs of Cushing's disease in order to make/assist in an early diagnosis.

Disease Prevalence According to the Cushing's Support and Research Foundation (CSRF), an estimated 10-15 people are affected by the condition per every 1 million births. While Cushing's may never be a major portion of an LPN's patient caseload, it is important for nurses to be aware of its characteristics because it can co-exist with any disability, disease, or syndrome. As such, LPNs may find themselves in positions to assist in recognizing the disease.

Both Cushing's disease and Cushing's syndrome exist, both of which are the result of incorrect production of the steroid hormone cortisol, a hormone normally made by the adrenal glands and referred to as the "stress hormone" because it's typically produced by the body in response to stress. When produced it increases blood pressure and blood sugar, and reduces immune responses.

According to CSRF, Cushing's syndrome occurs when a tumor on the adrenal glands causes secretion of too much cortisol. Cushing's syndrome can also be caused by medications such as prednisone, which can limit and/or halt the level of cortisol the body is able to produce.

Cushing's disease occurs when one produces too much of the adrenocorticotropic (ACTH) hormone, which stimulates the adrenal glands and causes them to make too much cortisol. ACTH-producing tumors can originate elsewhere in the body (such as on glands, chest, thyroid or pancreas), but are most often found on the pituitary gland in both men and women. These tumors are almost never cancerous.

My SurgeryI had transsphenoidal surgery to remove the tumor and the gland at the Cedars-Sinai Medical Center, Los Angeles, in spring 2007. The procedure is very delicate in nature but is most often recommended, according to the Pituitary Network Association. It's carried out through the use of microscopic instruments that are inserted into the nose or upper lip and through the sphenoid sinus. I now take hydrocortisone, synthroid and desmopressin acetate. The hydrocortisone is needed to replace cortisol in the absence of my pituitary gland. I take the synthroid for hypothyroid and desmopressin acetate for diabetes insipidus, which is a result of losing the pituitary. I also wear a medical alert bracelet and carry a medical identification card in my purse.

Despite the surgeries, I was back at work on a limited basis within 4 months. In spite of how all of this may sound, I never once experienced any pain. I never even had headaches (as some Cushing's patients report).

Ongoing RecoveryAccording to my doctors, total recovery has been documented to take up to 3 years. Now, 14 months post surgery, I still experience muscle weakness, fatigue and dry skin, but I consider myself healthy.

I do get very cold easily, so I always make sure I have a sweater when I go out, and I had lost 30 pounds 2 months post-surgery because I had no appetite, but I've since gotten 10 back. Additionally, my insulin intake has gone from 105 units per day to 8 units and my blood pressure medication has been cut in half, which brings me within normal limits. I've lost my moon face and buffalo hump. As a bonus, I rarely have to shave my legs. (Thick, course hair is characteristic of Cushing's, but with the surgery comes normal conditions.)

As an SLP of more than 25 years, I have found some language deficits in myself due to the surgery. These deficits include word retrieval, memory and "language of confusion." This confusion is worse on some days than on others and is characterized by interchanging the beginning or ending consonants of single words such as saying, "ford" or "chord" but meaning "board." It's weird, and I recognize it as it is happening and am sometimes able to self-correct it most of the time. I also practice many word-retrieval exercises, puzzles and watch old movies (which I love) to write down the actors, scenes, dialogue, etc., I can identify.

My concentration and word retrieval are also getting better and, today, I would judge these language deficits within 95 percent of where I was presurgery, unless I am very fatigued and it's difficult to concentrate.

Relating To LPNs I share this life experience with you and your fellow nurses because I want to implore you to be aware of your total patient. The root of someone's condition may not be what it appears to be. I was lucky because my Cushing's was originally suspected, not because of one individual characteristic but due to several seen together. I'm living proof that it can be cured.

Saturday, December 27, 2008

Purpose: Testosterone is the principal male sex hormone but is also present in smaller amounts and may be important in women. Among its likely actions in women are the building of bone and muscle mass, increase in interest in sex (libido) and effects on the mood. The role of testosterone replacement in women with low testosterone levels is currently being studied. In this study, you will be given an experimental preparation of a testosterone gel or placebo gel which will be applied on the skin of your outer thigh for 6 months. It is anticipated that this experimental gel application will produce levels of the drug in the normal range for women. You will get the testosterone gel for one year after the study, regardless of whether you were on testosterone gel or placebo gel during the study. You will also receive growth hormone without charge if it is determined that you are growth hormone deficient.

The aim of this study is to assess whether testosterone gel will improve body composition, muscle strength, thinking and sexual function in female patients with dysfunction of the pituitary gland. We will also carefully record side effects related to testosterone. It is expected that this study will determine if testosterone replacement is beneficial in women with pituitary dysfunction.

Friday, December 26, 2008

NEW YORK (Reuters Health) - Surgical removal of the kidney -- a procedure known as nephrectomy -- improves survival in patients with locally advanced renal cell carcinoma, the most common form of kidney cancer.

Dr. Pierre I. Karakiewicz from University of Montreal and colleagues determined survival rates for 43,143 patients treated with nephrectomy for advanced renal cell carcinoma that had not spread to other sites and a group of similar patients that did not have the surgery.

Death due to cancer was 5.8-fold higher for nonsurgical therapy than for nephrectomy, the team reports.

In a second analysis, where a subset of patients treated without surgery were matched with up to four surgically treated patients, there was still a 5.1-fold higher rate of cancer-specific mortality (death) in the nonsurgical group than in the nephrectomy group.

Overall, 5- and 10-year estimates of cancer-specific survival were 68.6 percent and 57.5 percent, respectively, for the nephrectomy group, compared with just 14.5 percent and 10.6 percent, respectively, for the nonsurgical therapy group.

This study, the investigators conclude, show that nonsurgical therapy is associated with a 44 percent to 57 percent worse survival than nephrectomy.

"Based on these findings, nephrectomy should be considered as the treatment of choice for patients with locally advanced renal cell carcinoma," they conclude.

(SACRAMENTO, Calif.) — Kidney cancer is typically without symptoms until it has spread to other organs, when it is also the most difficult to treat. Newer chemotherapies show great promise for extending survival during later disease stages, but they can also be highly toxic.

In one of the first discoveries of its kind, UC Davis Cancer Center researchers have identified ways to block a cancer gene's own repair mechanism and, in so doing, help make chemotherapy for kidney cancer more effective and better tolerated. The outcome is published in the current issue of Cancer Biology and Therapy."Cancer cells are notorious in their ability to rapidly create copies of themselves. While the latest medications slow down that process, they do not tend to be curative and have many side effects," said Robert Weiss, a UC Davis professor of nephrology and chief of nephrology at the Sacramento VA Medical Center. "We wanted to find ways to help make chemotherapeutics as effective as possible at the lowest doses possible."

Newer medications work by destabilizing cancer cells at the DNA level, which reduces their ability to replicate. Knowing that the p21 gene has an important role in restoring cancer cell DNA and potentially circumventing the benefits of those treatments, Weiss sought to identify compounds that could interrupt this pathway. The team tested thousands of compounds and 12 were found to bind to the recombinant protein p21. Additional tests showed that three of those compounds decreased p21 expression, blocking kidney cancer cells' ability to mend and making them more responsive to DNA-damaging treatments.

"The results are very exciting, especially given how difficult kidney cancer has so far been to treat," Weiss said. "Our work offers hope that in the future these p21 inhibitors can be refined and used in concert with other conventional as well as novel cancer treatments to increase the comfort and life spans of patients with kidney cancer."

For future studies, Weiss will focus on the three candidate compounds to determine the lowest possible concentrations at which they remain effective and to further optimize their anti-cancer properties. He will then test those compounds with standard treatments in animal models and, ultimately, in human trials.

"The goal is to find new approaches to treating a cancer for which few options currently exist and make those approaches available in clinical settings as quickly as possible," he said.

Other UC Davis study authors were See-Hyoung Park, Xiaobing Wang, Riuwu Liu and Kit Lam. Their research was supported by the National Cancer Institute, the U.S. Department of Veterans' Affairs, the Morris Animal Foundation, the National Institutes of Health and the National Science Foundation.

Designated by the National Cancer Institute, UC Davis Cancer Center's team of expert surgeons, medical oncologists and radiation therapists cooperate in the treatment of urological cancers. A strong research component drives the urologic cancer program, and active participation in national clinical trials gives our patients access to the newest treatment options. For more information, visit the cancer center Web site.

This is an observational study to confirm the presence of recurrent or persistent endogenous Cushing's syndrome in patients who have had primary surgical and/or radiation therapy for Cushing's disease and continue to manifest symptoms and signs of hypercortisolemia.

A Study to Confirm the Presence of Recurrent or Persistent Cushing's Syndrome in Patients With Clinical Signs or Symptoms of Hypercortisolemia Who Have Been Treated for Cushing's Disease

Further study details as provided by Corcept Therapeutics:

Primary Outcome Measures:

To confirm the presence of recurrent or persistent endogenous Cushing's syndrome in patients who have had primary surgical and/or radiation therapy for Cushing's disease and continue to manifest symptoms and signs of hypercortisolemia. [ Time Frame: up to 16 weeks ] [ Designated as safety issue: No ]

Arlene Ben-Zur has been to hell and back and has lived to write about it. Her journey is contained in a new book entitled Cancer of my Soul: A Personal Battle For Survival Against the Odds in which she retells the abuse she suffered at the hands of her late father and two ex-husbands, her battle with Cushing's disease and her painful separation from her granddaughter.

Ben-Zur began writing about her experiences in a journal three years ago. The process became a form of therapy for her. Over the course of three years she had enough material to put into a book. Her hope is that other women might see themselves in her story and avoid the pitfalls that she has suffered.

"If I can just touch one person's life with this so they won't go through what I went through, or maybe someone might read it and it will give them the impetus they need to change their situation, that would be amazing," says Ben-Zur.

Ben-Zur's heart-wrenching journey began when she had the misfortunate of being born after the death of her sister Shelley, who passed away from cancer at the age of three. Her own mother died of cancer when Ben-Zur was 15. Through it all she suffered a litany of physical and emotional abuse at the hands of her father, which eventually led her to try and commit suicide at 16.

"My father hurt me more than anyone else in my lifes," Ben-Zur writes in her book. "From my earliest memory, he expressed his dislike for me, despite the fact that I was at the top of my class, and well loved by my peers and teachers ... He told me over and over again that I was ugly, fat, stupid, and a slut, and that no one would ever love me."

Her two marriages, the first to a wealthy young man in New York, and the second to a Yemenite Jew in Israel, followed the same pattern as her relationship with her father. They were both incredibly abusive and destructive.

Even when she finally found true happiness with a man after her divorce from her second husband, it was destructive in that he was already married. When her lover's wife found out about their seven year affair, Ben-Zur made a clean break.

Around the same time she met her current partner Jamie and the pair have been together ever since. A year an half ago they moved to Orleans to escape the turmoil in Israel and live a more peaceful existence. Ben-Zur also had a chance to move next door to her childhood friend Marilyn Dow. The pair had promised each other years ago that if they ever had a chance to live next door to each other they would.

While Ben-Zur has lived through many traumas in her life, it hasn't all been bad. Her marriage to her first husband produced two daughters, Lee Anna and Rhonda and her second marriage resulted in the birth of her son Avi.

In an effort to get as far away from her first husband as possible, she moved to Israel where she opened a successful English school in Ber Sheba. Professionally, it was the most fulfilling and rewarding time of her life. But personally, she had to suffer through a second abusive marriage and the heartbreak of a doomed love affair before finally meeting her soul mate and eventually moving to Orleans.

Through it all, she has managed to keep a wonderful sense of humour and an incredibly positive outlook on life. Writing the book was both physically and emotionally draining, but now that it's finished she can now look forward to the future with hope.

"The most difficult part was reliving everything that had happened. I cried through every single page and every word," says Ben-Zur. "But once I finished it was like a huge weight had been lifted from my shoulders and now it's gone."

When she finished her manuscript she showed it to Raymond Coderre at Baico Publishing who instantly fell in love with it and agreed to publish it.

Ben-Zur now wants to try her hand at writing children's books and possibly get back into teaching, but first she has a date with someone very special. Her granddaughter's foster parents have allowed for the two to see each other for the first time in three years. Allie and her younger brother Matthew were put into foster care in Israel after Ben-Zur's daughter Rhonda had to be treated for mental illness following the birth of her second daughter.

The book is actually written as a type of letter to Allie, who Ben-Zur has only seen once since December 2004. The young girl is now eight.

While "Cancer of my Soul" will no doubt strike a chord with female readers, especially those who have been in an abusive relationship or have struggled with a life threatening illness, its message will resonate with anyone, male or female, who has the ability to feel compassion and empathy for their fellow man. It is exceptionally inspiring and reminds us all that the human spirit can conquer all.

Cancer of my Soul: A Personal Battle for Survival Against the Odds is available at the Baico Bookstore at 294 Albert Street (near Kent St.). It can also be ordered online by visiting www.baicopublishing.com.

Comments: MaryO has been THE person who has educated patients about Cushing's. She set up multiple websites, message boards, blogs, and more to help those who suffer with this disease. SHe is a true hero in my book.

she has helped so many of us learn about cushings. We have learned about everything from symptoms, to testing, and on to surgery, and what to expect after the surgery.. We now know alot more than some doctors, and we owe it all to Mary O. If it wasn't for her we still would be undiagnosed, as alot of doctors do not understand cushings at all. She made the wonderful websites for cushings, where you can go for information. The websites have taught me so much about cushings and is helping me in my fight for a diagnosis. I don't think there is ANYONE more deserving of this award than MARY O, she is just fantastic!!!!

Comments: Mary has helped spread the word about Cushings Disease and it has helped me immensely in getting to the right doctor, getting the right tests and finally getting over this horrible disease. She deserves to win.

Comments: MaryO has a great blog for Cushing's patients, their families and doctors. There is personal experience and madical research articles. Her blog does much to educate and support Cushing's patients.

Comments: I have known MaryO online for several years now. She has helped countless patients inform themselves and become advocates for Cushing's Syndrome/ Disease. She has formed an incredible support community of patients, friends and families or Cushing's patients--one like no other out there! Many of us owe our lives to her blog, website and message boards, because that is where we were able to find the information we needed in order to see the specialists who helped us to get well. And a plus, she's just plain awesome ass a person too!

Without the help of MaryO and her site I don't know if I would have ever found out what was wrong with me. MaryO is truly a hero to so many people here in the United States and around the world. How many people would spend there time, energy, finances and anything else they have to help people they don't know and may never, ever, see. She deserves this award and so much more.

Mary is a remarkable person. Despite her personal health issues, she is determined to help others improve the quality of their life by providing information and moral support.

Her efforts have provided an organized, informative and knowledgeable resource for individuals seeking help for the devastating effects of Cushings. One of the by products of her work has been life changing benefits for many who have been enabled to negotiate a very complex diagnostic process to get treatment.

~~~~~~~~~~~~~~~~~~~~~~

I am absolutely blown away by these wonderful comments. I've been feeling down and depressed for quite a while now and coming across these mean so much to me.

When I start asking “why me”, I turn to… Isaiah 6:8 Then I heard the voice of the Lord saying, “Whom shall I send? And who will go for us?” And I said, “Here am I. Send me!” ..and say “why not me”. Like the saying goes, “It is choice, not chance, that determines your destiny.” We control how we react to bad situations. Life isn’t about fair or unfair. Life is about the ability to choose. Some things, like cancer, cushing’s and life threatening illnesses give us little or no choice in the matter. Most of us do not raise our hand and say pick me. What we do have is the ability to choose on how we react to it and how we let it define us or rather, how we redefine ourselves after facing something tragic.

Over the last 25 years or so I've asked myself the same question, like most of us have, I'm sure. My dad was from the Why Not? school so I kind of leaned that way, too.

If someone had to get Cushing's why wouldn't it be me? But the main question is why anyone had to get Cushing's in the first place. It's not like a disease caused by bacteria or parasites where another organism is trying to live and prosper. Cushing's just is.

Did I get it because of my problem pregnancies or were did I miscarry because of yet-undiagnosed Cushing's?

What was the event that changed my life from relatively normal to that of a Cushie? Was it the hard whack on the back of my head? Doctors would never commit to that but I always wondered.

Was it related to my years of adult acne, my ever-present extra weight...or just because?

I'm sure I'll never know the answer to any of those questions without a doubt but I feel very sure that I was somehow selected to get Cushing's. When I had Cushing's, I'd never even touched a computer, let alone thought about websites but it just seemed that somehow it was meant to be that I go through Cushing's and create this site.

But why do any of us get this? Is it to fund doctors and surgeons? I think not but I don't know the answer. Why do our hormones go berserk on us? Why is one person cured with "only" one surgery while others require three, four, more? If 25% of all people have pituitary tumors why do only some of them cause Cushing's?

It's a puzzlement!

~~~~~~~~~~~~~

So...I was maybe "chosen" to have Cushing's. Why in the world did I get cancer on top of that? And why wasn't it colon cancer like all of my relatives?

I know one thing for sure - there's not going to be another website for kidney cancer!

Summary THE stress of myocardial infarction or surgery has been studied with sequential intravenous glucose tolerance tests for growth hormone, insulin, glucose and with 24-hour urinary epinephrine and norepinephrine assays. Elevated catecholamines were observed in all patients but were not specifically related to the observed growth hormone and insulin changes. Insulin was elevated initially in 60 per cent, and sluggish insulin responses were found initially in 40 per cent. Sixty-six per cent had elevation of growth hormone initially; sixteen per cent had a paradoxical growth hormone response initially, and two patients failed to respond to intravenous glucose. Plasma cortisols were more readily suppressed than plasma growth hormone. The inter-relationship of catecholamine, growth hormone, and insulin secretion are discussed. Biochemistry Dept. U.C.D.

It always seems that dogs have it better, at least in the Cushing's world. Easier and faster diagnosis; less severe treatment options. So today, another drug for dogs has been FDA approved. It would be nice if the FDA approved all these meds - or better ones! - for people. <sigh>

VETORYL Capsules contain the drug trilostane, which has been demonstrated to be effective in the treatment of Cushing's syndrome in dogs. VETORYL will be indicated for use in pituitary-dependent hyperadrenocorticism, which comprises the majority of cases of Cushing's syndrome in dogs. Additionally,VETORYL has received designation status as a Minor Use Drug for treatment of hyperadrenocorticism caused by adrenal tumors -- the first drug to receive an approval for this indication and the first drug to receive a Minor Use designation in dogs.

Mike Eldred, President of U.S. Operations, says, "We are very excited to have approval to market this novel product in the U.S. Following its launch in January, veterinarians will be able to source the product through our network of distribution partners."

It’s one of the most troubling trends in the current state of the health of our nation: childhood obesity. A particularly troubling condition because the extra pounds they put on now, often put children on the path to health problems that were once confined to adults, such as diabetes, high blood pressure and high cholesterol.

In certain rare cases, genetic diseases and hormonal disorders can predispose a child to obesity. These diseases, such as Prader-Willi syndrome and Cushing's syndrome, affect a very small proportion of children. In the general population, however, eating and exercise habits play a much greater role as the root cause of childhood obesity....

Thursday, December 11, 2008

"There is no doubt in my mind that medical professionals will now be inundated with women who are finally going to say, 'It's not my fork, it's my thyroid you need to test.' The first time I walked into an endocrinologist's office, I was expecting him to take one look at me and say, 'Oh, hormone issues, that's my specialty!' There were stories of a doctor in Los Angeles who could spot someone with Cushing's syndrome from across a crowded room. If you look up an endo's studies, you'll see thryoid, pancreas, adrenal gland, and hormones listed. If you talk to an endo, you'll hear, 'I don't think you have diabetes.' They seem to forget that they have more than one organ to study. Unfortunately, the patient has no say in this, and we are pushed out the door faster than you can say Nutrisystem."

Friday, December 5, 2008

The mission was to get the line cleared. And we succeeded. I must admit, however, I would not be eager to do this particular drill again.

We got it done, thanks to the power of prayer, some planning and a very resourceful surgeon. The surgeon, Dr.Sidney Guo, is a young Chinese man, who is also an accomplished violinist.

I liked him instantly; he reminded me of Michael.

Departing from the usual practice, we did the carotid artery operation without general anesthesia. This was done primarily so I could signal the surgeon immediately if anything broke loose.

In effect I was serving as another monitoring instrument. The operation went on for about two hours, During this entire time I was either conversing with or exchanging signals with the surgeon and his surgical nursing staff to keep them apprised of the fact that nothing had gone amiss.

The purpose of the operation to clear the carotid artery was to prevent any future TIA's. A TIA would require discerning the threat and responding within minutes. The down side of the surgical remedy was the fact that the operation could knock some plaque loose and thereby precipitate a stroke, disability or death.

I assured the surgeon that although I did not fear death, I was in no rush. In any event we decided to "go for it". Thanks to our resolve and steadiness, the surgeon's skill and the grace of God, we succeeded with this major operation under local anesthesia. Rounding out the plan, was a nap after the operation in the Recovery Room. And after my nap I was ready to go by 5 PM on Wednesday. Prayers are always welcome; even now when we are "out of the line of fire" and well along in the recuperation phase.

Dr. Guo came by Thursday morning to cut off the bandages and remove the drain. The surgical site was drained of about 30 or 40 cc's of blood during the night.

I walked in to the hospital at 8AM on Wednesday. The operation "teed up" at 9:30 AM Wed. and I walked out at Noon on Thursday.

All that remains now is a half dozen butterflies and some tape over the wound.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Thursday noon I made my escape from the hospital after a 30 hour marathon effort including a very successful operation.

Was helped by lots of prayers, which were very effective

I will be working from home on "light duty" probably through Monday.

If you ever need to know how it feels to be awake and alert and conversing with the surgeon during a major operation I can now tell you from first hand experience.

My left carotid artery was operated on yesterday morning. During the two hour operation I was totally awake and "working with" the surgeon. Through his questions to me and my responses and pre-arranged signals back to him and the surgical nurses, he could track "live and in real time" the effects on my brain and thinking ability of his excising, reconnecting and reinforcing a damaged spot in my left carotid artery.

An interesting experience. A close call. And a clear success. Deo gratias Onward Thanks

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Here is a walk through of some recent medical adventures, during which some valuable lessons were learned.

At the overview level the story is as simple as A, B, C A. A Transient Ischemic Attack (TIA) in 2006. A TIA is a temporary and mild stroke that passes within a short time: ranges from a few minutes up to a few hours.The TIA does no lasting damage to the brain. A stroke however does inflict lasting damage up to and including death. A TIA is a warning sign that something is amiss. A TIA may be followed by a stroke, particularly if the TIA prompts no changes.

In 2006 in response to the urging of a friend, I reluctantly went to the Emergency Room about 2.5 hours after a TIA started. Generally we have about 3 hours to respond to a TIA or stroke. I wasted 2.5 hours in denial and delay. In 2006 I made four classic mistakes: 1. not recognizing the TIA, 2. denying it was happening, 3. dismissing it as unimportant and 4. delaying the response of going to the ER to get help.

I did two things right: 1. I was, and still am, lucky 2. I listened to a friend who insisted I should go to the ER and should do so now. She probably saved my life either in 2006 or 2008 or both.

The take away was: 1. I now knew what a TIA was; 2. I had a good set of 2006 base line tests (MRI, Echocardiogram, Carotid Doppler and so on) from the tests the ER people did. 3. I also now knew where to find an ER that could handle strokes. It was Fair Oaks Hospital; convenient, new and well equipped, with well trained staff who were ready. B. I Learned about TIA, strokes, etc. 2006- 2008 Doctors, books, newsletters, hospital literature, Internet and so on C. A second Transient Ischemic Attack (TIA) on Nov 2, 2008. Because of the learning that occurred after the 2006 TIA I knew how to detect it, how to preliminarily diagnose it and how to take preventive and remedial action.. Again the TIA came and went with no adverse effects.

But this time I decided to follow through and correct the underlying situation. Preliminary diagnosis of TIA or stroke is simple. Here are three tests that are easy to do when we sense a TIA might be underway:

1. Smile looking in a mirror. If your smile is asymmetric (drooping down on one side) take an aspirin at once and go immediately to an Emergency Room equipped to handle strokes

2. Raise both arms. If you can not you failed the test and should go immediately to the ER

3. Say a simple sentence like "No ifs ands or buts" If any part of the sentence is garbled or unclear you should go immediately to the ER

Failing any one of these tests is a signal to get to the Emergency Room. Within two minutes of sensing the onset of the TIA at about 6:40 AM on that Saturday morning I had done these three tests. Within three minutes I had taken two aspirin and awakened Mary. Within 5 minutes I was on my way to the Fair Oaks ER. Within 15 to 20 minutes from the onset of the TIA I was in the Fair Oaks ER. The aspirin I took within two minutes knocked down the TIA within the first hour. That stabilized the situation and we then made contact with the ER staff. The ER doctors, nurses and tech staff repeated all the tests that we had done in 2006. Now we had the 2006 baseline and a second 2008 reading.

Again we were lucky and there was no lasting damage. However, this additional info persuaded me to take corrective action and started me on a round of preparation including seeing my family physician, getting his referrals to specialists, interviewing surgeons, doing tests and finally scheduling the surgery for Dec 3, 2008. The surgery to clear a carotid artery blockage was successful. The improvement was immediate and dramatic. To prepare for and consolidate these gains we are now well underway on a new regimen of medication,diet and exercise.

Some of this info may be helpful to you and others. Feel free to share it. The penalty for either not recognizing a TIA; or not knowing what to do; or not doing it can be severe, up to and including disability and death. I was lucky in 2006;

...I was ready and lucky in 2008

Was also praying more in 2008; that always helps.

Having been lucky twice, the new game plan is to move proactively to prevent any recurrence. Onward,

Context: Midnight salivary cortisol (MSC) is now recognized as a reliable index for Cushing’s syndrome diagnosis but has to be validated for the follow-up of treated patients.

Objective: Our objective was to evaluate MSC for assessing the outcome of transsphenoidal surgery (TSS) in patients with Cushing’s disease (CD).

Design: We conducted a retrospective cohort study in a single center.

Patients and Methods: Sixty-eight patients treated by TSS between 1996 and 2006 and followed for at least 6 months with postoperative MSC were included. Mean follow-up (± SD) was 45 ± 31 months. Morning plasma cortisol was determined 5 d after TSS, and MSC and urinary cortisol (UC) were determined 6–12 months after surgery. The remission group included hypocortisolic (morning plasma cortisol < 50 ng/ml and/or insufficient response to cosyntropin) and eucortisolic (midnight plasma cortisol < 75 ng/ml and normal UC) patients. Patients in the treatment failure group had high midnight plasma cortisol and UC concentrations.

Results: Fifty patients (74%) were in remission. Mean MSC was 0.7 ± 0.4 ng/ml (range, 0.4–2.1 ng/ml) and 6.5 ± 6.5 ng/ml (range, 2.1–27.2 ng/ml) for the remission and treatment failure groups, respectively (P = 0.001). A cutoff of 2 ng/ml for MSC gave a sensitivity of 100% and a specificity of 98% for treatment failure diagnosis, whereas UC less than 90 µg/d had a sensitivity of 71% and specificity of 98%. Postsurgical morning plasma cortisol less than or equal to 18 ng/ml had a sensitivity of 93% and specificity of 74%.

Conclusions: MSC is a simple, robust marker of remission after TSS for CD.

My husband is having surgery in less than 12 hours. He seems unconcerned. I'm terrified. I can't talk to him about it because he'd say it was ok, he's going to live forever. Yadda Yadda.

But I can't help myself. All these scary scenarios keep running through my mind and it disturbs me. I haven't been afraid of my own surgeries. Why does his scare me? Was he maybe afraid when I had mine but we didn't talk about it?

12 hours from now I hope to be posting that all is well, he's better than ever, going to get out of the hospital sooner than planned.

I'm saying my prayers and have people praying for him and for me. Maybe it's always harder on the person who isn't the patient, the one who waits for the good news while trying to stay calm.

So now I try to sleep, so I can be calm tomorrow, ready for whatever news the surgeon brings.

Yesterday was so long, tiring, hunger-inducing, maddening, yet a blessing!

We got up early to be at the hospital by 7:30 am. We were a "tad" late, of course, so I dropped DH off at the front door to fend for himself with the paperwork. I found a parking place right where I always parked when he had his initial incident. WooHoo.

This parking lot is very terrible. They're tearing it up to put in another medical building and a parking garage. The garage will help eventually but now it makes parking a nightmare. Some of the staff has to park at my church and be shuttled over.

So, we got to the waiting room, tastefully decorated with monitors showing a tropical fish tank and a gas fireplace. Very soothing. Not!

But it wasn't too long before he was called back. The nurse, Doris, was very nice and we actually had a few laughs and it was kind of pleasant - for me, anyway.

There was a moment of fear when the vampire was putting in the IV. She wanted to do the right side because his surgery was going to be on the left. He wanted the right side. They had quite a discussion about that and I was afraid that DH might change his mind and we'd just go home. He won, though, with the caution that they might have to change it when he got into surgery.

The pastor from my church came in and we had a nice discussion that ranged from diabetes and the inability to give himself the shots to the Roman Catholic Church to the combat engineers.

The anesthesiologists came in had DH practice with the squeaky toy he'd need to use during surgery to show that they hadn't cut any vital nerves or anything really important. I don't know where they found it but it was a dog toy that looked like a head with brains spilling out over the top. EEEWWWWWWWWWW

The surgeon came in just at 9 and reminded us of all the possible things that could go wrong. All my worst fears. My minister prayed, I gave DH (not the minister!) a kiss and he was gone.

M and I went back to the waiting room. He sat with me a while and asked me if I'd eaten and I said no but it was ok. I didn't usually eat until 2-3 or so. After a while he left and i went to the bathroom. While I was in there, my friend showed up and was asking the desk folks where I was and they didn't know (of course). So, she turned around and there I was. Amazing.

We went to the cafeteria - good thing! but they only had donuts, bagels, coffee, a little fruit since it was so early. It was getting close to 11 and the surgeon said it would take about 2 hours so, after glancing quickly at the craft fair in the lobby, we went back to the waiting room. As promised, the surgeon came out about 11:20 and said that everything went well. DH did have to have a drain but that was ok. That the plaque was hemorrhagic. They got all the gunk cleared out and everything was looking fine. Great!

I called everyone I'd said I'd call to give the good news of a successful surgery. Yea!

So, my friend and I chatted for awhile, waiting to go see DH. And chatted. And waited. And chatted...

I went to the desk to see why I wasn't going back. They said he probably didn't have a room yet.

We chatted and waited some more. 2PM Doris came out to talk to another patient. She said she'd see what was up with DH. Never saw her again.

More chatting, waiting. Asked another staff person who said maybe DH was too dizzy (?), he was still in Recovery One. Whatever.

Friend had to leave. It was about 3.

About 3:30 I called and left a message that I might not make bell rehearsal that night. I was tired, hungry, hadn't even seen DH yet, was sure the dog was really messing up the house.

Surgeon came out from another surgery wand asked why I was still there. I told him and he said that 4 hours in recovery was standard for this surgery. I said that no one had told me that. I could have eaten, gone home to walk the dog, not been worrying about what was happening in the back. That PO'd me just a bit.

There were only 3 of us left in the waiting room and it was getting dark. Finally, about 5, they told me he was in a room. I gathered my stuff up and found him on the 5th floor.

He looked good except for the bandage on his neck and the drain. We talked for a while and he wanted a book so I said I'd go home and get it and take the dog out etc.

Amazingly, the dog hadn't done anything in the house at all. She's only 6 months old and I was amazed at her self-control. I took her out, gave her a little dinner while I tracked down the book. I had a handful of honey almonds (most nut-ritious!) and a bit of stale coffee.

Back to the kitchen for her, back to the hospital for me. This time it was very hard finding a parking place - and my gas was getting very low.

DH was in his room chomping down dinner. We went for a little walk around the perimeter of the floor and that was kind of tiring. Talked for a bit. He's going to slow down and work less. We're going to travel more. I've heard all this before so I nodded and said uh huh when appropriate. We'll see.

About 8 or he was fading so I left. I could have turned left out of the hospital and gone to the end of rehearsal but i didn't. I went right and to the grocery store where I got 2 small bags of chips and a sub - and some real stuff.

I took the puppy out again, gave her dinner, called my best friend. We talked for about an hour, me sipping some wine. I had my 2 bags of chips, my sub, finished my wine and zonked out, exhausted.

He's coming home today. The drains, IVs and all are out now, I think. I have to go back in about half an hour to get him or to wait for the discharge papers.

Then, I'll bring him home, get settled, and head off to my temporary job. After about 7 tonight I can sleep. Yea!

Then, tomorrow I pick up my Mom to take her to the dentist and the next round begins...

Wednesday, November 26, 2008

Diagnosing and treating Cushing’s syndrome is sometimes just as difficult as it was 70 years ago.

For as long as it has been described, Cushing’s syndrome has presented physicians with a problem. Harvey Cushing first described it in 1932, and the diagnosis, differential diagnosis and treatment of Cushing’s have remained a major challenge for endocrinologists ever since.

Though uncommon, it is difficult to consider Cushing’s syndrome a rare occurrence. New research has shown Cushing’s syndrome to have a substantially higher prevalence than previously thought. Unexpected endogenous hypercortisolism may occur in 0.5% to 1% of patients with hypertension, 2% to 3% with poorly controlled diabetes, 6% to 9% with incidental adrenal masses and 11% with osteoporosis and vertebral fractures.

“We are gaining an appreciation that Cushing’s is more common than it was once believed to be,” said Mary Ruppe, MD, endocrinologist at the University of Texas Health Science Center at Houston, and program committee chair of the Women in Endocrinology organization. “This fact points to the need for data regarding the value of the different diagnostic approaches and for data regarding treatment/outcomes in populations with Cushing’s.”

As most of the characteristics of Cushing’s are common in the general population, including obesity, depression and hypertension, it is extremely difficult for endocrinologists to decide on who should be screened for the disorder. A recent clinical review by Hershel Raff, PhD, and James W. Findling, MD, noted that as the number of patients in these high-risk groups continues to increase, the need for a sensitive and specific diagnostic test for Cushing’s syndrome has become paramount.

The three most commonly performed diagnostic studies for Cushing’s syndrome — urine-free cortisol, low-dose dexamethasone suppression test and the nocturnal salivary cortisol — are also not without hurdles. All three have been shown to produce false positives and false negatives.

Shlomo Melmed

Approximately 80% of patients with Cushing’s syndrome have an adrenocorticotropic-secreting neoplasm from a pituitary tumor (Cushing’s disease) or a nonpituitary neoplasm, and the treatment of Cushing’s disease remains challenging for both endocrinologists and neurosurgeons as well. Transsphenoidal surgery is currently the standard treatment of choice in patients, but achieving surgical remission has been difficult as well.

“Cushing’s syndrome is a very rare but important diagnosis for the patient and endocrinologist. Confirming the diagnosis may be challenging, and before embarking on a costly set of tests, the endocrinologist should be reasonably assured that the patient indeed requires diagnostic exclusion by rigorous screening methods,” said Shlomo Melmed, MD, senior vice president of Academic Affairs at Cedars Sinai Medical Center, Los Angeles, and an Endocrine Today editorial board member.

With more than 7.5 decades of research since Dr. Cushing’s discovery, what are the best methods of diagnosis and treatment for Cushing’s syndrome? Endocrine Today talked with leading researchers in the field to uncover the current trends in Cushing’s syndrome treatment.

Screening process

Laurence Katznelson, MD, is Associate Professor of Medicine and Neurosurgery at Stanford University, and Medical Director of the Pituitary Program at Stanford Hospital and Clinics.

Photo by Norbert Von der Groeben

Laurence Katznelson, MD, associate professor of medicine and neurosurgery at Stanford University, and medical director of the pituitary program at Stanford Hospital and Clinics, explained to Endocrine Today the difficulty of deciding who should be screened for Cushing’s syndrome. For instance, although the syndrome is associated with multiple comorbidities, including obesity, hypertension and depression, endocrinologists should be prepared to delve a little deeper into the symptoms to see if they warrant a screening test.

“The presence of Cushing’s syndrome should be considered if these medical conditions are present, though diagnostic testing should be performed only in subjects who have signs favoring Cushing’s, such as demonstration of objective proximal weakness, spontaneous ecchymoses and violaceous striae,” Katznelson said.

“For example, central obesity with supraclavicular and dorsicervical fat pads would favor a diagnosis of Cushing’s syndrome, in contrast to the presence of generalized obesity,” he said.

“There is no clear guideline,” said Roberto Salvatori, MD, associate professor of medicine in the division of endocrinology at Johns Hopkins University School of Medicine. “You need to keep your mind open.”

“Sometimes Cushing’s is obvious. Sometimes, when it is mild, it may not be diagnosed for many years. One must screen a lot of patients to find one with Cushing’s. However, anytime a physician thinks about the possibility of a patient having the disease, work-up should be initiated,” he said.

Testing options

Opinions varied when Endocrine Today asked researchers which of the three tests for Cushing’s syndrome was most reliable.

“No test is 100% sensitive or specific,” Salvatori said. “I always use two, sometimes three, screening tests.” However, Salvatori noted he feels the night-time salivary cortisol test is the most reliable and easy to obtain.

Raff and Findling described the measurement of free cortisol in a 24-hour urine collection as being long considered the gold standard for the diagnosis of endogenous hypercortisolism. The test relies on the concept that as daily production of cortisol is increased, the free cortisol filtered and not reabsorbed or metabolized in the kidneys will be increased. They noted that current research has shown that many patients with mild Cushing’s syndrome do not have elevations of urine-free cortisol, “making it a poor screening test for this condition.”

The low-dose dexamethasone suppression test relies on the concept that the correct dose of dexamethasone will suppress ACTH, and cortisol will release in normal patients while patients with corticotroph adenomas will not suppress below a specified cut off. Raff and Findling noted that because of the significant variability of the biological behavior of corticotroph adenomas, research has shown that neither the overnight 1-mg dexamethasone suppression test nor the two-day low-dose dexamethasone suppression test appears to be reliable using the standard cutoffs for serum cortisol.

According to Raff and Findling, there is no diagnostic test used in the evaluation of Cushing’s syndrome that performs better than the late night/midnight salivary cortisol method. The concept is based on the fact that patients with mild Cushing’s syndrome fail to decrease cortisol secretion to its nadir at night. However, they still acknowledged that many factors, such as stress, sleep disturbances and psycho-neuroendocrine may falsely elevate nocturnal cortisol secretion.

“Because each of these tests has associated false positives and negatives, a combination of these tests is often necessary for a valid diagnosis,” Katznelson said. “In the end, these tests need to be considered in the context of a history and physical examination that favors this diagnosis.”

Lynette Nieman, MD, associate director of the Intramural Endocrinology Training Program at the NIH, agreed. “Of the three recommended tests, each is useful in certain conditions,” she said. “I try to stress that the testing should be individualized since some tests are likely to be falsely positive in some situations, eg, a woman on birth control pills is likely to have a high corticosteriod-binding globulin, which might elevate serum cortisol.”

Ruppe said the choice between the tests should be based on patient characteristics that will allow for adequate collection of each sample. “For instance, the use of a late-night salivary cortisol measurement would be suboptimal in an individual who works the third shift and may not have an intact circadian rhythm, or the choice of a 24-hour urinary free cortisol may be suboptimal in an individual with urinary frequency or urinary incontinence.”

Ruppe also noted that one possible improvement would be to improve standardization of the assays across different labs. “Since there is no standardization, the quality of the performance of the assay can vary across different facilities and centers,” she said.

Petrosol sinus sampling

Another controversial topic in the field is whether or not the inferior petrosol sinus should be sampled for an ACTH gradient to distinguish between Cushing’s disease and occult ectopic ACTH syndrome.

The invasive procedure has proven to be relatively safe when performed by experienced radiologists, but not all medical centers have the capability.

A woman with mild hypercortisolism, a normal or slightly elevated plasma ACTH and normokalemia has an approximately 95% likelihood of having Cushing’s disease before any differential diagnostic testing is performed, according to Raff and Findling. In contrast, a male patient with prodigious hypercortisolism of rapid onset, hypokalemia and marked elevations of plasma ACTH may be more likely to have an occult ectopic ACTH-secreting tumor.

About half of patients with ACTH-secreting microadenomas are estimated to have a normal pituitary MRI. In such situations, it is important to perform further testing, particularly an inferior petrosal sinus catheterization, to discern the presence of an ectopic ACTH-producing lesion, according to Katznelson.

“Some people would say that every patient should have it because it is the one best test for the differential diagnosis of ACTH-dependent Cushing’s syndrome,” Nieman said. “However, patients in whom data strongly suggest Cushing’s disease might forego it.”

“In a young woman with an MRI with a definitive adenoma and high-dose dexamethasone test showing less than 60% suppression, it is reasonable to proceed with surgery,” Salvatori said. “But even the International Prostate Symptom Score is not 100% sensitive or specific.” Raff said that he disagrees with the high-dose dexamethasone test.

Transsphenoidal surgery

Currently, transsphenoidal surgery is the primary treatment of Cushing’s disease associated with an ACTH-secreting pituitary tumor. According to recent studies, remission rates after transsphenoidal pituitary microsurgery range from 42% to 86%.

Raff told Endocrine Today that the most important treatment recommendation that an endocrinologist makes to a patient with Cushing’s disease is referral to a neurosurgeon with extensive experience.

“Referral to a neurosurgeon who is highly experienced in this procedure is critical,” Katznelson agreed. He noted that there have been studies demonstrating that both the degree of tumor bulk resection and rates of biochemical remission are increased for all types of pituitary tumors when the surgery is performed by a neurosurgeon with extensive experience in endonasal pituitary surgery.

“In Cushing’s disease, this is especially true,” Katznelson said. “Because the tumors in this disorder are often small, if not microscopic, the surgical strategy may require dissection through the gland. In inexperienced hands, this may result in higher rates of hypopituitarism and lower rates of biochemical cure,” Katznelson said.

“There is no doubt that the surgeon’s experience influences the success rate,” Nieman said.

Constantine Stratakis, MD, with the National Institute of Child Health and Human Development, said he agreed, and stressed the importance of confirmation of diagnosis of Cushing’s syndrome prior to a referral to a neurosurgeon.

“There is nothing worse than an inexperienced surgeon operating on a patient with Cushing’s or a surgeon operating on a patient who does not have a firm diagnosis of Cushing’s syndrome,” Stratakis said.

“Surgery offers a reasonable chance for cure in the hands of an experienced neurosurgeon,” said Amir Hamrahian, MD, a staff physician at the Endocrinology Institute at the Cleveland Clinic. “We are currently involved in two studies looking at new medications for medical treatment of patients with Cushing’s syndrome. However, surgery is still the best initial approach for those not cured,” Hamrahian said.

The future

“Medications are the future for patients with inoperable, recurrent Cushing’s syndrome,” Stratakis said, referring to pasireotide (SOM230), a somatostatin analog.

He was part of a study in 2006 examining the in vitro effects of SOM230 on cell proliferation in human corticotroph tumors. Researchers found SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. They concluded that SOM230 may have a role in the medical therapy of Cushing’s disease. Raff said he believes that clinical trials in patients with Cushing’s disease who used SOM230 were not particularly successful. Anne Klibanski, MD, director of the neuroendocrine clinical center at Massachusetts General Hospital and primary investigator of the study, commented that in vitro studies play a critical role in assessing novel targeted pituitary tumor therapies. It is only in rigorous clinical trials that the overall efficacy and risks of such therapies can be established, she suggested.

“Microsurgical improvements will also be significant, but the major problem right now is the number of patients who are left untreated with recurrent disease,” Stratakis said. “For them, there are very few options other than irradiation, so innovative medical treatments with molecularly designed compounds or targeted to specific receptors and/or functions of the pituitary are the most important advances that I see coming in the near future,” Stratakis said.

According to James Liu, MD, assistant professor of neurologic surgery at Northwestern University Feinberg School of Medicine in Evanston, Ill., the future appears bright in the battle against Cushing’s.

Katznelson said he hopes the future will bring improved diagnostic strategies important for detecting true Cushing’s syndrome in the presence of multiple comorbidities. He noted that the ongoing research studies involving innovative medical therapeutic strategies that target the corticotroph adenoma itself, or block the effects of cortisol in the periphery, should bring new treatment options in the future.

“These studies will hopefully lead to novel medical options for this syndrome,” Katznelson said. “There have been significant advances in surgery, particularly with the development of minimally invasive, endoscopic surgery that has resulted in both improved biochemical outcomes and patient tolerability.” – by Angelo Milone

About Me

I am a Cushing's patient who has dealt with Cushing's symptoms since 1983 (or earlier) and the aftereffects of pituitary surgery since 1987.

Because I had very little support for my symptoms, diagnosis and surgery, I decided to try to make things a little better for other patients and started a support site called Cushing's Help and Support in 2000. The site has grown to astronomical numbers. This disease isn't as rare as doctors have told us!

In 2006, I was also diagnosed with kidney cancer (renal cell carcinoma). My left kidney and adrenal gland were removed. Having an adrenal gland removed complicates my post-Cushing's symptoms.